Overall Summary/Abstract The Case Cancer Disparities P20 proposal provides for planning and development of a Specialized Program of Research Excellence (SPORE) in cancer health disparities. This proposal places an emphasis on colon adenoma, precursor lesion of colorectal cancer (CRC), and on breast cancer, which are the two leading causes of cancer death in the United States, and of which, racial disparities persist and are widening. This proposed P20 program builds on the resources of the Case Comprehensive Cancer Center to propose two cutting edge translational Research Projects that use multi-level risk assessment approaches for examining racial difference and epigenetic aging in the development of early colon neoplasia (Project 1) and use systems biology approaches for interrogating molecular mechanisms underlying racial disparities in triple negative breast cancer (TNBC) response to treatment and survival (Project 2). These two Research Projects each are built upon substantial preliminary data, cutting edge technology and methodology, and enabling patient cohorts and tissues to test novel hypotheses with high translational significance. This P20 program will further develop a comprehensive infrastructure for catalyzing a robust Developmental Research Program (DRP) that extend our efforts to other cancers and socioeconomic, demographic and behavioral factors contributing to cancer disparities. A series of 2 core resources support these projects and also establish a strong programmatic infrastructure for transdisciplinary translational research in cancer health disparities. The proposal brings together a highly transdisciplinary team of investigators that work collaboratively through every stages and aims of the proposed research studies to accomplish the translational goal of this P20 application.